CN105030841A - Application of Akkermansia muciniphila BAA-835 strain - Google Patents
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Abstract
Description
技术领域 technical field
本发明属于益生菌的应用领域，特别涉及AkkermansiamuciniphilaBAA-835菌株在治疗或预防糖尿病方面的应用。 The invention belongs to the application field of probiotics, in particular to the application of Akkermansiamuciniphila BAA-835 bacterial strain in treating or preventing diabetes.
背景技术 Background technique
由于现代人生活方式及饮食结构的改变，糖尿病的发病率日益增加。糖尿病作为心血管事件、肿瘤等的发病危险因素，已成为一个全球性的社会健康问题。目前，针对糖尿病的，除了传统的五架马车及糖尿病后期应用胰岛素外，并没有长期有效的治疗手段。自2004年GORDON实验室提出肠道菌群作为一个环境因子可以调节脂代谢后，近年来肠道菌群与肥胖及糖尿病的相关性研究层出不穷。2012年，深圳华大利用基于鸟枪法测序的新一代测序技术对345个中国人的肠道标本进行了测序分析，发现患有2型糖尿病的患者存在明显的肠道菌群失调，表现为产丁酸盐的菌群丰度减低同时伴有机会致病菌增多。这些都可能成为鉴别2型糖尿病的标志和潜在的治疗靶点。基于小鼠体内的研究发现了一些可以降低血糖的细菌类型，如LactobacillusrhamnosusGG。该该篇文章采用db小鼠灌胃的给药方式，分别给予无菌生理盐水或细菌悬液，每天灌胃，持续4周,记录体重情况，试验结束后测小鼠糖耐量。结果表明该细菌持续灌胃可以改善db小鼠的糖代谢及体重增加。这些研究的发现为开发益生菌干预糖尿病提供了重要试验依据和技术手段。 Due to the changes in the lifestyle and diet structure of modern people, the incidence of diabetes is increasing day by day. As a risk factor for cardiovascular events and tumors, diabetes has become a global social health problem. At present, there is no long-term effective treatment for diabetes, except for the traditional five carriages and the application of insulin in the late stage of diabetes. Since the 2004 GORDON laboratory proposed that intestinal flora can regulate lipid metabolism as an environmental factor, research on the correlation between intestinal flora and obesity and diabetes has emerged in an endless stream in recent years. In 2012, Shenzhen Huada used the next-generation sequencing technology based on shotgun sequencing to sequence and analyze the intestinal samples of 345 Chinese people, and found that patients with type 2 diabetes had obvious intestinal flora imbalance, manifested as production Bacterial abundance in butyrate decreased and opportunistic pathogens increased. All of these may become markers for identifying type 2 diabetes and potential therapeutic targets. Studies based on mice have identified some types of bacteria that can lower blood sugar, such as LactobacillusrhamnosusGG. This article adopts the method of gavage administration of db mice, respectively giving sterile normal saline or bacterial suspension, and gavage each day for 4 weeks. The body weight is recorded, and the glucose tolerance of the mice is measured after the experiment. The results showed that continuous gavage of the bacteria could improve the glucose metabolism and weight gain of db mice. The findings of these studies provide an important experimental basis and technical means for the development of probiotics to intervene in diabetes.
发明内容 Contents of the invention
本发明的目的是提供AkkermansiamuciniphilaBAA-835菌株在制备治疗或预防糖尿病方面中的应用，涉及治疗或预防糖尿病的药物、药物组合物、食品及饲料等方面的应用。该菌株降低小鼠血糖，改善小鼠的糖代谢。拓宽了AkkermansiamuciniphilaBAA-835菌株的使用范围，开发了一种有效的、新的、无毒副作用的治疗和预防糖尿病的应用领域。 The object of the present invention is to provide the application of Akkermansiamuciniphila BAA-835 strain in the preparation of treatment or prevention of diabetes, which relates to the application of medicines, pharmaceutical compositions, food and feed for treatment or prevention of diabetes. The strain reduces blood sugar and improves glucose metabolism in mice. Widen the scope of use of Akkermansiamuciniphila BAA-835 strains, and develop an effective, new, non-toxic and side effect-free application field for the treatment and prevention of diabetes.
本发明涉及AkkermansiamuciniphilaBAA-835菌株在制备治疗或预防糖尿病药物中的应用。经过实验证明，AkkermansiamuciniphilaBAA-835菌株具有降低小鼠血糖，改善小鼠糖耐量的有益效果，所以，该菌株是糖尿病干预的益生菌，可以应用在制备治疗或预防糖尿病的药物中。 The invention relates to the application of Akkermansiamuciniphila BAA-835 strain in the preparation of medicines for treating or preventing diabetes. Experiments have proved that the Akkermansiamuciniphila BAA-835 strain has the beneficial effects of reducing blood sugar and improving glucose tolerance in mice. Therefore, this strain is a probiotic for diabetes intervention and can be used in the preparation of drugs for treating or preventing diabetes.
一种治疗或预防糖尿病的药物组合物，其特征在于，包括：AkkermansiamuciniphilaBAA-835菌株以及药学上可接受的辅料。优选的，该治疗或预防糖尿病的药物组合物为固态时，所述药物组合物中包含107－1012cfu/g的AkkermansiamuciniphilaBAA-8352菌株。 A pharmaceutical composition for treating or preventing diabetes, characterized by comprising: Akkermansiamuciniphila BAA-835 strain and pharmaceutically acceptable auxiliary materials. Preferably, when the pharmaceutical composition for treating or preventing diabetes is solid, the pharmaceutical composition contains 10 7 -10 12 cfu/g of Akkermansia muciniphila BAA-8352 strain.
该治疗或预防糖尿病的药物组合物为液态时，所述药物组合物中包含107－1011cfu/mL的AkkermansiamuciniphilaBAA-835菌株。 When the pharmaceutical composition for treating or preventing diabetes is in a liquid state, the pharmaceutical composition contains 10 7 -10 11 cfu/mL of Akkermansia muciniphila BAA-835 strain.
所述药学上可接受的辅料为选自载体、赋形剂、稀释剂、润滑剂、润湿剂、乳化剂、悬浮液稳定剂、防腐剂、甜味剂以及香料中的至少一种。经过动物实验，该药物组合物可以治疗或预防糖尿病。 The pharmaceutically acceptable adjuvant is at least one selected from the group consisting of carriers, excipients, diluents, lubricants, wetting agents, emulsifiers, suspension stabilizers, preservatives, sweeteners and spices. Through animal experiments, the pharmaceutical composition can treat or prevent diabetes.
上述药物组合物可以制备成治疗或预防糖尿病的药物。优选的，所述药物为颗粒剂、胶囊、片剂、粉末剂、口服液、混悬液和乳剂中的至少一种制剂形式。 The above pharmaceutical composition can be prepared as a medicine for treating or preventing diabetes. Preferably, the medicine is in at least one formulation form of granules, capsules, tablets, powders, oral liquids, suspensions and emulsions.
一种治疗或预防糖尿病的食品，其特征在于，包括AkkermansiamuciniphilaBAA-835菌株以及食品学上可接受的辅料。优选的，所述治疗或预防糖尿病的食品为固态时，所述食品中包含107－1012cfu/g的AkkermansiamuciniphilaBAA-835菌株。 A food for treating or preventing diabetes is characterized in that it includes Akkermansia muciniphila BAA-835 strain and food acceptable auxiliary materials. Preferably, when the food for treating or preventing diabetes is solid, the food contains 10 7 -10 12 cfu/g of Akkermansia muciniphila BAA-835 strain.
该治疗或预防糖尿病的食品为液态时，所述食品中包含107－1011cfu/mL的AkkermansiamuciniphilaBAA-835菌株。 When the food for treating or preventing diabetes is in a liquid state, the food contains 10 7 -10 11 cfu/mL of Akkermansia muciniphila BAA-835 strain.
所述食品学上可接受的辅料为选自载体、赋形剂、稀释剂、润滑剂、润湿剂、乳化剂、悬浮液稳定剂、防腐剂、甜味剂以及香料中的至少一种。 The food acceptable auxiliary material is at least one selected from the group consisting of carriers, excipients, diluents, lubricants, wetting agents, emulsifiers, suspension stabilizers, preservatives, sweeteners and spices.
一种治疗或预防糖尿病的饲料，其特征在于，包括AkkermansiamuciniphilaBAA-835菌株以及饲料学中可接受的辅料。 A feed for treating or preventing diabetes is characterized in that it includes Akkermansiamuciniphila BAA-835 bacterial strain and acceptable auxiliary materials in feed science.
本发明的有益效果为：本发明提供了AkkermansiamuciniphilaBAA-835菌株在制备治疗或预防糖尿病药物中的新用途，通过实验，验证了AkkermansiamuciniphilaBAA-835菌株对血糖控制非常有效，而且灌菌小鼠糖耐量曲线下面积比对照组小鼠减低了21.3％。所以，AkkermansiamuciniphilaBAA-835菌株可以用于治疗或预防糖尿病的药物、药物组合物、食品及饲料中，拓宽了AkkermansiamuciniphilaBAA-835菌株的应用领域。 The beneficial effects of the present invention are: the present invention provides a new application of the Akkermansiamuciniphila BAA-835 strain in the preparation of medicines for the treatment or prevention of diabetes. Through experiments, it has been verified that the Akkermansiamuciniphila BAA-835 strain is very effective in blood sugar control, and the glucose tolerance curve of the mice filled with bacteria The lower area was reduced by 21.3% compared with the control mice. Therefore, the AkkermansiamuciniphilaBAA-835 strain can be used in medicines, pharmaceutical compositions, food and feed for treating or preventing diabetes, which broadens the application field of the AkkermansiamuciniphilaBAA-835 strain.
附图说明 Description of drawings
图1是小鼠灌菌5周后，糖耐量对比图。 Figure 1 is a comparison chart of glucose tolerance in mice after 5 weeks of infusion.
图2是小鼠灌菌5周后，糖耐量曲线下面积对比图。 Figure 2 is a comparison chart of the area under the glucose tolerance curve after 5 weeks of feeding mice with bacteria.
具体实施方式 Detailed ways
下面结合实施例，对本发明作进一步说明： Below in conjunction with embodiment, the present invention will be further described:
本实施例中用到的小鼠模型为：选取10周龄C57/BL6雄性SPF级小鼠，均从上海斯莱克动物实验有限公司购买。小鼠5只一笼饲养于隔离包中，自由进水进食，维持昼夜节律。 The mouse model used in this example is: select 10-week-old C57/BL6 male SPF mice, all purchased from Shanghai Slack Animal Experiment Co., Ltd. Five mice were housed in a cage in an isolation bag, with free access to water and food, and to maintain a circadian rhythm.
菌株信息：AkkermansiamuciniphilaBAA-835菌株购买自美国ATCC公司，产品名称：AkkermansiaBAA-835。 Strain information: Akkermansia muciniphila BAA-835 strain was purchased from ATCC, USA, product name: Akkermansia BAA-835.
实施例1 Example 1
将C57/BL6雄性SPF级小鼠同窝随机分成对照组和灌菌组，每组8-10只，对照组给予无菌PBS灌胃，每天一次；灌菌组给予AkkermansiamuciniphilaBAA-835菌株悬液按照2*109cfu/只小鼠，进行灌胃试验，每天一次。试验5周。试验结束后，检测小鼠糖耐量情况。 The C57/BL6 male SPF mice were randomly divided into the control group and the bacteria-filled group, with 8-10 mice in each group. The control group was given sterile PBS, once a day; the bacteria-filled group was given Akkermansiamuciniphila BAA-835 strain suspension according 2*10 9 cfu/mouse, intragastric administration test, once a day. Test for 5 weeks. After the experiment, the glucose tolerance of the mice was detected.
具体糖耐量情况如下表1的所示。 The specific glucose tolerance is shown in Table 1 below.
表1 Table 1
从表中可以看出，对小鼠进行AkkermansiamuciniphilaBAA-835菌株悬液灌胃后，糖耐量明显比对照组的小鼠增加缓慢，说明AkkermansiamuciniphilaBAA-835菌株对血糖的控制非常有效。具体如图1和图2所示。 As can be seen from the table, after intragastric administration of the Akkermansiamuciniphila BAA-835 bacterial strain suspension to the mice, the glucose tolerance was significantly slower than that of the mice in the control group, indicating that the Akkermansiamuciniphila BAA-835 bacterial strain is very effective in controlling blood sugar. Specifically shown in Figure 1 and Figure 2.
对小鼠的糖耐量曲线下面积进行了计算，具体如表2所示： The area under the glucose tolerance curve of the mice was calculated, as shown in Table 2:
表2 Table 2
从表2中可看出，给予小鼠AkkermansiamuciniphilaBAA-835菌株悬液灌胃后，灌菌组小组的糖耐量曲线下面积降低了21.3％，说明AkkermansiamuciniphilaBAA-835菌株对小鼠血糖的降低效果非常有效。 It can be seen from Table 2 that after intragastric administration of the Akkermansiamuciniphila BAA-835 strain suspension in mice, the area under the glucose tolerance curve of the bacteria-infused group group was reduced by 21.3%, indicating that the Akkermansiamuciniphila BAA-835 strain is very effective in reducing blood sugar in mice .
以上所述为本发明的较佳实施例而已，但本发明不应该局限于该实施例所公开的内容。所以凡是不脱离本发明所公开的精神下完成的等效或修改，都落入本发明保护的范围。 The above description is only a preferred embodiment of the present invention, but the present invention should not be limited to the content disclosed in this embodiment. Therefore, all equivalents or modifications that do not deviate from the spirit disclosed in the present invention fall within the protection scope of the present invention.
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9486487B2 (en) | 2014-10-31 | 2016-11-08 | Whole Biome Inc. | Methods and compositions relating to microbial treatment and diagnosis of disorders |
| CN107043714A (en) * | 2016-12-13 | 2017-08-15 | 广州康泽医疗科技有限公司 | A kind of probiotics and preparation method thereof |
| CN110201003A (en) * | 2012-02-29 | 2019-09-06 | 伊西康内外科公司 | The composition of microbiota and relative method |
| CN110638838A (en) * | 2018-06-26 | 2020-01-03 | 深圳月曜生命科技有限公司 | Application of Ackermansia or prevotella in preparing medicine for enhancing anti-tumor immunity |
| CN110693917A (en) * | 2019-07-16 | 2020-01-17 | 江苏省中医院 | Application of Akkermansia Muciniphila in preparation of antidepressant or health-care product |
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